ESTROGEN-RELATED RECEPTOR ALPHA IS IN- VOLVED IN THE REGULATION OF MITOFUSIN 2 EX- PRESSION IN ADRENOCORTICAL HUMAN CELLS

KATIA E. HELFENBERGER; ANA FERNANDA CASTILLO; YANINA BENZO; GIULIANA ARGENTINO; PAULA MALOBERTI; CECILIA PODEROSO

Congreso; LXIII Reunión Anual de la Sociedad Argentina de Investigación Clínica (SAIC); 2018

Mitofusin 2 (Mfn2) is a mitochondrial protein that participates inmitochondrial fusion, protects against apoptosis and activates mi-tochondrial metabolism in mammalian cells. Mfn2 expression isdownregulated in obesity and in type 2 diabetic patients and muta-tions in this protein cause neurodegenerative diseases, like Char-cot-Marie-Tooth type 2A neuropathy. It has been described thatMfn2 gene expression regulation involves several transcriptionfactors. Mfn2 can be induced directly by the cooperative action ofPPAR-γ coactivator-1α (PGC-1α) and estrogen-related receptor-α(ERRα). We have previously shown in adrenocortical human cellsthat Angiotensin II (Ang II) regulates Mfn2 expression by increasingits mRNA and concomitantly its mitochondrial localization. The aimof this work was to study the role of ERRα on the regulation of Mfn2expression in adrenal cells. We observed in H295R adrenocorticalhuman cells that stimulation with Ang II modulates ERRα protein ina time-dependent manner. Then, we demonstrated by qPCR thatERRα overexpression increases Mfn2 mRNA in control and in AngII-stimulated cells (Mock vs. ERRα: 1 vs. 4.51, Mock + Ang II vsERRα + Ang II: 5.46 vs. 8.77 ***p